Domain structure of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a glycoprotein of the endoplasmic reticulum.
Domain structure of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a glycoprotein of the endoplasmic reticulum.
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DOI：
10.1016/s0021-9258(18)89764-2
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发表时间：
1985-01
期刊：
影响因子：
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通讯作者：
Laura Liscum;J. Finer-Moore;Robert M. Stroud;K. Luskey;M. Brown;J. L. Goldstein
中科院分区：
文献类型：
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作者：
Laura Liscum;J. Finer-Moore;Robert M. Stroud;K. Luskey;M. Brown;J. L. Goldstein
我们提出并评估了3-羟基-3-甲基戊二酰辅酶a还原酶的二级结构和膜取向模型，该酶是内质网的糖蛋白，控制胆固醇的生物合成速率。该模型来源于蛋白水解实验，该实验将97千道尔顿酶分离为两个结构域，nh2末端膜结合结构域339个残基和cooh末端水溶性结构域548个残基，该结构域延伸到细胞质中并包含催化位点。这些结构域是通过与分子中特定区域对应的合成肽的抗体反应来鉴定的。基于分子克隆确定的氨基酸序列，还原酶结构的计算机模型预测，nh2末端结构域包含7个跨膜区域。基因结构分析表明，每个拟议的跨膜区域编码在一个单独的外显子中，并被一个内含子与相邻的跨膜区域隔开。预计还原酶的cooh末端结构域包含两个β结构，两侧是一系列两亲螺旋，它们可能共同构成活性位点。还原酶的nh2末端膜结合结构域与视紫红质有一些相似之处，视紫红质是视网膜棒盘的光感受器蛋白，也是唯一已知氨基酸序列的细胞内糖蛋白。
We present and evaluate a model for the secondary structure and membrane orientation of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the glycoprotein of the endoplasmic reticulum that controls the rate of cholesterol biosynthesis. This model is derived from proteolysis experiments that separate the 97-kilodalton enzyme into two domains, an NH2-terminal membrane-bound domain of 339 residues and a COOH-terminal water-soluble domain of 548 residues that projects into the cytoplasm and contains the catalytic site. These domains were identified by reaction with antibodies against synthetic peptides corresponding to specific regions in the molecule. Computer modeling of the reductase structure, based on the amino acid sequence as determined by molecular cloning, predicts that the NH2-terminal domain contains 7 membrane-spanning regions. Analysis of the gene structure reveals that each proposed membrane-spanning region is encoded in a separate exon and is separated from the adjacent membrane-spanning region by an intron. The COOH-terminal domain of the reductase is predicted to contain two beta-structures flanked by a series of amphipathic helices, which together may constitute the active site. The NH2-terminal membrane-bound domain of the reductase bears some resemblance to rhodopsin, the photoreceptor protein of retinal rod disks and the only other intracellular glycoprotein whose amino acid sequence is known.